tbuckley/cabot-search huggingface dataset:
Real-world data: Clinical characteristics and outcomes of patients with advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab in Veteran Health Administration.
Authors: Munaf Alkadimi, Kana Lucero, Lauren Diaz Boyle, Maria Elena Fierro, Kathleen Franklin, Zohra Nooruddin, Michael Mader
Journal: Journal of Clinical Oncology (2023)

2651 Background: Advanced Hepatocellular carcinoma (HCC) is an aggressive tumor, and most patients have a poor prognosis. Recent clinical trials have demonstrated improved survival with molecularly targeted treatment and immunotherapy. Atezolizumab plus Bevacizumab (A+B ) is the recommended first-line treatment for advanced HCC based on the phase 3 IMbrave 150 trial. However, in a real-life setting, many patients do not meet the inclusion criteria of this landmark trial. This study proposes a retrospective review of outcomes of advanced HCC patients receiving A + B in Veterans Health Administration (VHA). Methods: Patients with advanced HCC receiving 1st line systemic therapy with A+ B at the VHA between Dec 1, 2019, to Mar 1, 2022, were selected from the electronic medical records (EMR) using ICD-9 and ICD-10 codes. Abstractors reviewed EMR and followed from their index date of A+ B initiation until death or their last VHA visit, with the study period ending on Jan 31, 2023. The Chi-Squared test was used to compare rates, and the Mann-Whitney test was used to compare medians. Results: A total of 332 patients met the study criteria. The median age was 67 yrs., 99% were males, 63% non-Hispanic White, 26% were Black, 66 % had ECOG ≥ 1, 84% had CPS class A, 16% had CPS class B and C, 62% had grade 2 ALBI score, 56% had viral hepatitis-caused HCC, 80 % had cirrhosis, and 67% had prior local therapies. The outcomes are shown. Conclusions: In our real world, despite having similar PFS as the phase 3 IMbrave 150 trial, our OS at 12 months was lower (52% vs. 67%), given that we had more elderly patients with moderate liver dysfunction and 40% were non-white. This study provides actual outcomes in clinical practice where patients do not match the study population of the pivotal trial. [Table: see text]
Change in quality of life of metastatic breast cancer patients seeking treatment at Komfo Anokye Teaching Hospital, Ghana.
Authors: Anita Eseenam Agbeko, Adelaide Bekae, Jonathan Boakye-Yiadom, Joshua Arthur
Journal: Journal of Clinical Oncology (2023)

e24111 Background: Despite developments in breast cancer screening for early diagnosis and treatment, 20-85% of women go on to develop distant metastasis, based on tumor biology, stage at presentation and treatment modalities received. The primary goal of treating metastatic breast cancer (MBC) is to improve quality of life (QoL). This study assessed the change in QoL for patients with MBC seeking treatment at Komfo Anokye Teaching Hospital (KATH). Methods: Women with MBC seen at KATH had QoL assessed using the Functional Assessment of Cancer Therapy Breast (FACT-B) questionnaire before, and 3 months after they were supposed to have received systemic treatment - chemotherapy, hormonal, target therapy. Data was analyzed using STATA v17 software. The higher the FACT scores, the better the QoL. Results: Fifty-six women with MBC were interviewed. Their mean age was 51.7 years. Only 27 (48%) of them received some systemic treatment – chemotherapy, hormonal, target therapy – over the study period. Baseline median QoL scores in the wellbeing domains were physical (PWB) = 17.5, social/family (SWB) = 16.0, emotional (EWB) = 12.0, functional (FWB) = 8.0, breast cancer subscale (BCS) = 22.0. Their median total QoL scores were FACT-B = 77.5; FACT-B TOI = 48.5 and FACT-G = 54.5. At follow up, 28 (50%) of participants were alive. About a third (9/28) of them received no systemic treatment. Of the remaining 19; 4, 1 and 14 received one, two and three cycles of systemic treatment respectively. Their median QoL scores were PWB = 20.5, SWB = 16.0, EWB = 16.0, FWB = 15.0, BCS = 22.5, FACT-G = 72.0, FACT-B = 94.5, and FACT-B TOI = 61.0. Fourteen had improved, and 14 had deteriorated QoL. The median minimally important difference (MID) for the improved QoL group was MID FACT-B = -22, MID FACT-B TOI = -10 and MID BCS = -4, and for the deteriorated QoL group was MID FACT-B = 26.9, MID FACT-B TOI = 18 and MID BCS = 5. Being dead at follow up was related to receiving no treatment (AOR = 6.97, CI: 1.91 – 25.47, p-value = 0.003) and having one metastatic site at baseline (AOR = 5.23, CI:1.43 – 19.12, p-value = 0.01). Conclusions: Mortality among women with MBC was high (50%), especially among those who did not receive any systemic treatment or had one metastatic site. Of the survivors, equal proportions had significantly improved and significantly deteriorated QoL scores albeit varying treatment courses received. Further studies are needed to explore how systemic treatment or not impact QoL changes and survival outcomes of MBC patients in KATH.
PD-L1 in head and neck cancers: Audit for tertiary care centre in India.
Authors: Zoya Ravish Peelay, Neha Mittal, Vijay Maruti Patil, Ajaykumar Chandrabhan Singh, Vanita Noronha, Kumar Prabhash, Nandini Sharrel Menon, Minit Jalan Shah
Journal: Journal of Clinical Oncology (2023)

e14565 Background: There is no data on the expression of Programmed Death Ligand 1 (PD-L1) in Head and Neck cancers (HNC) from the Indian population. Hence, this audit was done to estimate the incidence of PD-L1 expression in HNC’s and to detect factors affecting the same. Methods: Data was collected from 466 cases who were advised for PD-L1 gene expression testing from the HNC OPD of Tata Memorial Hospital, Mumbai. Ethics committee approval for this retrospective audit was obtained. Tumor Proportion Score (TPS) scoring for PD-L1 expression was performed using the VENTANA SP263 PD-L1 Assay. PD-L1 status was determined by the percentage of tumor cells with any membrane staining above the background. The demographic details and factors such as Eastern Cooperative Oncology Group (ECOG) performance status (PS), tobacco use, site of tumor, histopathology and time of biopsy. Descriptive statistics were used for analysis. Factors affecting PD-L1 gene expression were sorted using logistic regression analysis. Results: 466 patients were evaluated with a median age of 49 years (Range:16-85), PD-L1 expression was divided as scores and was observed that TPS-0% (Tumor proportion score) was seen in 73 patients (15.7%), TPS &gt;0-20% was seen in 174 patients (37.3%), TPS &gt;20-50% was seen in 88 patients (18.9%) and TPS &gt;50% was seen in 131 patients (28.1%). Higher expression of PDL-1 was seen in oral cavity as site of tumor (p=0.000), squamous cell histology (p=0.000) and consumption of tobacco (p=0.001). Conclusions: This is one of the first studies evaluating real world data on the expression of PDL-1 in HNC’s in the Indian population and factors affecting it. PDL1 expression of 1% or more is seen in 84.3% of HN cancers in India. The histology of the tumor is the major impacting factor. The data provides novel insight into many factors affecting the expression of PDL-1 in HNC’s and in the future can be of help in developing treatment plans with various immunotherapies. [Table: see text]
Prognostic impact of baseline circulating extracellular vesicles (BCEVs) in the setting of patients with advanced non-small cell lung cancer (ANSCLC) eligible for first line treatment with osimertinib.
Authors: Valerio Gristina, Nadia Barraco, Simona Taverna, Mauro Manno, Samuele Raccosta, Maria Lamantia, Anna Paola Carreca, Lorena Incorvaia, Giuseppe Badalamenti, Antonio Galvano, Viviana Bazan, Antonio Russo, Ignazio Ugo Carreca
Journal: Journal of Clinical Oncology (2023)

e14553 Background: In the liquid biopsy era, the interrogation of extracellular vesicles (EVs) content might be complementary for cancer prognostication and response assessment. In this explorative study, we aimed to describe whether the serial characterization of BCEVs plasma tumor-derived EVs could longitudinally reflect response and resistance to available first-line treatments, investigating the potential to predict clinical outcomes in patients with advanced NSCLC (aNSCLC). Methods: From 2020/02 to 2022/05, 27 treatment-naïve patients with aNSCLC (stageIIIB/IV), eligible for first-line treatment with an EGFRTKI (Osimertinib) or ICIs (e.g. Pembrolizumab ± platinum‐based chemotherapy) based on the predictive molecular pathology, were enrolled. Blood samples (∼5 mL) were collected into K2EDTA tubes early in the morning with fasting condition. We isolated EVs from 2 ml of plasma using exo-Easy Maxi Kit (Qiagen-USA). EVs’s size and distribution was determine by use of Dynamic Light Scattering method (DLS). Besides a Bradford assay (cfEV) for the indirect quantification of EV amount based on EVs proteins content was performed. According to the radiologic response, EV analyses were evaluated in patients with available plasma samples from baseline (T0) to the first radiologic evaluation of disease within 12 weeks (T1). Results: From 2020/02 to 2022/05, 27treatment-naïve patients with aNSCLC (stageIIIB/IV), eligible for first-line treatment with an EGFRTKI (Osimertinib) or ICIs (e.g. Pembrolizumab ± platinum‐based chemotherapy) based on the predictive molecular pathology, were enrolled. Blood samples (∼5 mL) were collected into K2EDTA tubes early in the morning with fasting condition. We isolated EVs from 2 ml of plasma using exo-Easy Maxi Kit (Qiagen-USA). EVs’s size and distribution was determine by use of Dynamic Light Scattering method (DLS). Besides a Bradford assay (cfEV) for the indirect quantification of EV amount based on EVs proteins content was performed. According to the radiologic response, EV analyses were evaluated in patients with available plasma samples from baseline (T0) to the first radiologic evaluation of disease within 12 weeks (T1). Conclusions: This real-world study confirmed the in vivo feasibility of isolating and characterizing BCEVs via DLS and Bradford assay from the plasma of patients with ANSCLC. The quantitative changes of the plasma EVs correlated with survival in the real-time monitoring of such first-line patients, mostly in the oncogene-addicted population receiving osimertinib.
Retrospective analysis on association of ABO blood type and immune checkpoint inhibitor response.
Authors: Akshee Batra, Rohit Singh, Samantha R Schuetz, Helen Gandler, Derek Devine, Jacob Barker, Hibba tul Rehman, Shahid Sattar Ahmed
Journal: Journal of Clinical Oncology (2023)

2596 Background: The presence or lack of a collection of antigenic cell surface markers on red blood cells makes up the ABO blood groups that contribute to various immunogenic neoantigens. Variations in the T-cell diversity and HLA haplotype with different blood types might affect a patient's response to Immune checkpoint inhibitors (ICIs). However, the association between the ABO blood type and ICIs is not well studied. Methods: We did a retrospective observational study to investigate the influence of ABO blood groups on patients receiving ICIs at the University of Vermont Cancer Centre. We examined the medical records of people who received ICIs as first-line therapy between January 2017 and June 2022 and collected demographic data, including age, sex, ethnicity, cancer stage, type and metastasis. We looked at overall survival and the occurrence of immune-related adverse events (irAEs) in different blood type subgroups and calculated relative risks. Results: A total of 288 cases were identified, out of which 169 had documented blood type, including 75 with A, 19 with B, 72 with O and 3 with AB blood type. The mean age was 63.71 years (Standard deviation (SD): 11.52), 58.6% were males, and ethnicity was 94.7% White, 1.2% Asian and 0.6% Hispanic. Lung cancer was most commonly identified at 41%, and 60% of total cancers were stage 4. The median ECOG status was 1 and the Charlson comorbidity index was 6. 36% of cases developed irAEs, whereas mortality was 39% during the study period. The relative risk of irAEs with blood type A and B compared to O was 0.89 and 0.83, respectively but wasn't statistically significant. The relative risk of irAEs of AB compared to O blood type was statistically significant at 2.63 (CI: 1.95-3.54). The relative risk of death in A and B blood types compared to O wasn't statistically significant. No patients in the AB blood group died. Conclusions: Clinically significant association wasn't found between different blood types and irAEs or mortality except for the increased risk of irAEs with AB compared to O. With the rapidly growing use of ICIs, prospective trials are needed to better understand the true risk of developing irAEs in patients with AB blood type. [Table: see text]
A phase 0 pharmacokinetic trigger trial of infigratinib in patients with recurrent high-grade glioma.
Authors: Nader Sanai, Tigran Margaryan, Jennifer Molloy, Anita DeSantis, Jocelyn Harmon, Amy Hong, Kelly Braun, John Wanebo, Wonsuk Yoo, An-Chi Tien, Artak Tovmasyan, Shwetal Mehta
Journal: Journal of Clinical Oncology (2023)

2051 Background: This Phase 0 trial evaluates tumor pharmacokinetic (PK) and pharmacodynamic (PD) responses of fibroblast growth factor receptor (FGFR) inhibitor, infigratinib, in participants with recurrent high-grade glioma carrying FGFR1 K656E or FGFR3 K650E mutation or FGFR3-TACC3 translocation. Patients with high unbound drug concentrations in the gadolinium-nonenhancing tumor region were graduated to a therapeutic regimen of infigratinib. Methods: Recurrent high-grade glioma patients received 7 days of infigratinib (125 mg QD) prior to planned resection at 7-9 hours following the last dose. Tumor tissue (enhancing and nonenhancing regions), cerebrospinal fluid (CSF), and plasma were collected. Total and unbound infigratinib concentrations were measured using validated LC-MS/MS methods. A PK ‘trigger’ determined eligibility for the therapeutic expansion phase and was defined as unbound [infigratinib] &gt; 5-fold biochemical IC50 (i.e., 5 nM) in non-enhancing tumor. PD response was assessed by quantification of percentage of positive pERK, MIB-1, and Cleaved Caspase 3 cells in the surgical tissue compared to baseline archival/biopsy tissue. Patients with tumors exceeding the PK threshold for unbound drug concentration were eligible for expansion phase therapeutic dosing of infigratinib. Results: Seven patients were enrolled into the Phase 0 study with 3 patients who met the PK threshold continued to the expansion phase. In non-enhancing tumor region, the mean unbound concentration of infigratinib was 3.5 nM (n=7). The mean non-enhancing tumor-to-plasma coefficient for unbound drug (Kp,uu) was calculated to be 1.4. The suppression of pERK levels and MIB-1 levels was observed in 17% (1/6) and 67% (4/6) of the patients, respectively. At a median follow-up of 16.3 months [range: 2.8-18.7 months], the median progression-free survival (PFS) was 2.8 months (n=3). One patient remains on treatment. No grade 3+ toxicities were observed, and no adverse events resulted in discontinuation of therapy. Conclusions: Despite relatively high unbound tumor-to-plasma (Kp,uu) value, infigratinib achieves sub-optimal unbound drug concentration in the non-enhancing brain tumor tissue. Pharmacodynamic response with archival tissue as comparator did not reveal inhibition of pERK. Clinical trial information: NCT04424966 .
Pattern of failure and re-irradiation for stereotactic radiotherapy treated brain metastases from non-small cell lung cancer (NSCLC).
Authors: Dayu Xu, Jiuang Mao, JianJiao Ni, Zhengfei Zhu
Journal: Journal of Clinical Oncology (2023)

e14010 Background: Hypofractionated stereotactic radiotherapy (SRT) has been increasingly used for brain metastases (BMs) from non-small cell lung cancer (NSCLC). However, the prognostic factors, pattern of failure and clinical utility of re-irradiation for these patients remain have not been fully understood. Methods: Metastatic NSCLC patients receiving SRT that covering all of the intracranial tumor lesions and without prior whole brain radiotherapy (WBRT) were retrospectively enrolled. Local recurrence free survival (LRFS), intracranial progression free survival (iPFS) and overall survival (OS) were calculated from the initiation of SRT. Post intracranial progression survival (OS2) was measured from the initial intracranial disease progression. Results: From 2018/07 to 2022/05, 218 patients were identified, with 142 (65.1%) having only one BM and 76 (34.9%) harboring 2-5 BMs. With a median follow-up of 31.1 (range, 1.0-44.6) months, median LRFS, iPFS and OS was 39.1, 26.6 and 31.1 months, respectively. No statistical difference of LRFS, iPFS and OS were found between patients with different numbers of BM. Nevertheless, patients receiving concurrent systemic therapy had significantly longer LRFS (HR=0.35, p=0.002), iPFS (HR=0.57, p=0.044) and OS (HR=0.37, p=0.001), when compared with those receiving SRT alone. By now, intracranial disease progression (iPD) was documented in 59 patients, with original site PD (OPD), new site PD (NPD) and both sites PD (BPD) occurring in 20 (33.9%), 17 (28.8%) and 22 (37.3%), respectively. Among the 59 patients, 19 (32.2%) received second-course SRT (re-SRT) targeting the intracranial progressive tumor lesions and re-SRT led to improved OS2 (22.7 vs 12.1 months, HR=0.29, 95%CI 0.08-0.97, p=0.045), which remained as an independent prognostic factor after multiple-variate Cox analyses. Conclusions: The status of systemic therapy, but not the number of BMs, may impact the survival outcomes of SRT-treated BMs from NSCLC. Some patients may benefit from re-SRT, which warranted future validation.
Dynamic monitoring of ctDNA to predict response to immunotherapy plus chemotherapy in BTC.
Authors: Chen Liu, Mingzhe Xiao, Yingjun Wu, Jianyang Ao
Journal: Journal of Clinical Oncology (2023)

e14550 Background: The survival of advanced BTC patients, especially those who received palliative surgery was unfavorable and the treatment options for these patients were limited. Immune checkpoint inhibitors （ICIs） were approved for the treatment for patients with BTC. However, only a subset of patients benefits from this treatment and the clinical performance was not well evaluated. Therefore, there is a need for a method that can promptly and dynamically evaluate the efficacy of patients receiving immunotherapy. Previous studies have shown that ctDNA can detect relapse and monitor therapeutic efficacy in diverse cancer. We performed a retrospective observational study examining whether ctDNA could serve as a biomarker to track treatment responses in BTC. Methods: Patients diagnosed with advanced BTC and who received ICI were screened and enrolled between January 2020 and October 2022 at Shanghai Eastern Hepatobiliary Surgery Hospital. The key inclusion criteria for patients were as follows: a recent diagnosis of gallbladder/intrahepatic cholangiocarcinoma; received immunotherapy (or plus target therapy); received ctDNA NGS monitoring. Patients were excluded based on the following criteria: patients with multiple primary cancers, or had history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation, or HIV infected person, or severe infections with poor clinical control. Blood samples were collected for ctDNA analysis at the beginning, after 3 and 6 months of ICI treatment. Results: The median age was 66 (42-79), and 12 (44.4%) were male. The ECOG score was mostly 1 (23 cases, 85.2%). Most of the patients were stage IV (21, 77.8%), and there were 5 (18.5%) stage III patients, 1 (3.7%) stage II and 0 (0%) stage I patients. The BTC patients were mostly histologically diagnosed with gallbladder cancer (GBC, 11, 40.7%) and intrahepatic cholangiocarcinoma (8 cases, 29.63%). There were 55% patients received palliative surgery. Among all mutations detected in ctDNA, the mutation status of KRSA at baseline was detected to be related to patient survival, and the KRAS-mut group had a significantly lower probability of overall survival compared to the KRAS-WT group (p=0.014). Patients with more than 3 new mutations during treatment presented a significantly unfavorable OS (p=0.025) and a trend of unfavorable PFS (p=0.062). Besides, patients with increasing amounts of total ctDNA during dynamic monitoring showed significantly worse overall survival probability (p=0.023). Conclusions: Mutation of KRAS in tissues at baseline might be a predictive marker of response to immunotherapy and survival prognosis. ctDNA as a compose biomarker can monitor treatment responses and predict overall survival. Considering the small size and the relatively short follow-up time of our cohort, further prospective and randomized controlled studies are indispensable.
Dysregulation of immune checkpoint proteins in patients with newly diagnosed early breast cancer undergoing neoadjuvant chemotherapy: A comparison between patients with triple negative breast cancer (TNBC) and non-TNBC.
Authors: Teresa Smit, Bernardo Leon Rapoport, Helen C. Steel, Carol Benn, Simon Nayler, Liezl Heyman, Annette J. Theron, Nomsa Hlatswayo, Luyanda LI Kwofie, Pieter Meyer, Ronald Anderson
Journal: Journal of Clinical Oncology (2023)

e14546 Background: Checkpoint proteins regulate the immune system. Breast cancer is associated with up-regulation or down-regulation of these proteins to evade anti-tumor immune responses. Soluble forms of immune checkpoint molecules (sICMs) can be measured in human plasma. The study aimed to measure the systemic levels of a series of co-stimulatory and co-inhibitory ICMs at diagnosis, post-neo-adjuvant chemotherapy (NAC) and post-surgery in newly- diagnosed BC patients (pts) and compare the biological behaviour of these sICMs between TNBC and non-TNBC patients. Methods: Soluble ICMs were measured using multiplex bead array technology in plasma from 72 BC pts and 45 healthy controls. Data were prospectively obtained and levels were compared between pre-treatment, post-NAC, and post-surgery using non-parametric tests (Mann-Whitney &amp; Kruskal-Wallis). Results: Following NAC, the plasma levels of six soluble co-stimulatory checkpoints (CD28, CD40, ICOS, CD27, CD80, GITR), all involved in the activation of CD8+ cytotoxic T cells, were significantly increased (p &lt; 0.04-p &lt; 0.00001). Four of the soluble co-inhibitory checkpoints (LAG-3, PDL1, TIM-3 and HVEM) increased significantly post-NAC, reaching levels significantly greater than those of the control group. PD-1 remained unchanged, while BTLA and CTLA-4 decreased significantly (p &lt; 0.03 and p &lt; 0.00001, respectively). Normalization of soluble co-stimulatory immune checkpoints seemingly indicates a reversal of systemic immune dysregulation following the administration of NAC in early BC. In contrast, recovery of immune homeostasis may explain the increased levels of several negative checkpoint proteins, albeit with the exceptions of CTLA-4 and PD-1. No significant differences were detected between the changes of 16 sICMs levels at pre-NAC, post-NAC and post-surgery when comparing the TNBC and non-TNBC patients. Conclusions: This study demonstrates low levels of co-stimulatory and co-inhibitory sICMs in newly-diagnosed, non-metastatic BC pts. Following treatment with NAC, the sICMs levels increase substantially, except CTLA-4. In the case of co-stimulatory sICMs, these novel findings are indicative of an immune-restorative mechanism. The pattern of co-inhibitory sICMs (elevated levels of PD-L1, LAG-3, TIM-3 and HVEM), might be indicative of immune-therapeutic resistance, underscoring the augmentative immune-therapeutic promise of targeting these molecules, either individually or in combination, to improve the outcome of pts with early BC. These differences were not significant between TNBC and non-TNBC patients.